Daxx interacts with and modulates the activity of CREB

Yen Sung Huang, Che Chang Chang, Tien Chi Huang, Yung Lin Hsieh, Hsiu Ming Shih

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8 Citations (Scopus)

Abstract

The phosphorylation of cAMP response element-binding protein (CREB) induced by the cAMP-dependent protein kinase A (PKA) elicits the recruitment of CREB-binding protein (CBP) for activating cAMP responsive gene expression. Several reports indicate that proteins binding to CREB and/or CBP play important roles in modulating the CREB-dependent transactivation. Here, we show that Daxx interacts with CREB and modulates CREB-mediated transcription. Daxx was identified as a CREB-interacting protein by a yeast two-hybrid screen. Depletion of endogenous Daxx by specific shRNA or overexpression of Daxx resulted in decreased or increased levels of the cAMP/PKA-induced reporter activity and target gene expression, respectively. In vitro and in vivo binding studies revealed that Daxx C-terminal domain binds to CREB basic leucine zipper domain. The binding of Daxx to CREB correlates with its repressive effect on a CRE-mediated reporter activity induced by forskolin or PKA. Furthermore, the results of electrophoresis mobility shift assays and chromatin immunoprecipitation experiments showed that Daxx attenuated the DNA binding potential of the CREB. Our study provides a previously undescribed role of Daxx in repressing cAMP-responsive gene expression and also a mechanism underlying the repressive effect of Daxx on CREB transcriptional potential.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalCell Cycle
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

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Keywords

  • cAMP-responsive-element-binding protein (CREB)
  • Death-associated protein 6 (Daxx)
  • PKA
  • SUMO-interacting motif
  • Sumoylation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Huang, Y. S., Chang, C. C., Huang, T. C., Hsieh, Y. L., & Shih, H. M. (2012). Daxx interacts with and modulates the activity of CREB. Cell Cycle, 11(1), 99-108. https://doi.org/10.4161/cc.11.1.18430